tbuckley/cabot-search huggingface dataset:
Abstract 14137: SARS-CoV-2 Spike Protein-Induced Inflammation Underlies Proarrhythmia in COVID-19
Authors: Louisa Mezache, Gerard Nuovo, David Suster, Esmerina Tili, Hamdy M Awad, Przemyslaw Radwanski, Rengasayee Veeraraghavan
Journal: Circulation (2022)

Cardiac manifestations are common in severe Coronavirus disease 2019 (COVID-19) with rates reported from 2% in non-ICU patients to 59% in non-survivors. Recent CDC data show that COVID-19 patients are at 1.7 higher risk of arrhythmia. AF, which is the most common arrhythmia, is a frequent complication of acute and long COVID-19. It has been reported that the SARS-CoV2 receptor, ACE2, is highly expressed in the heart, leading to the prevalent assumption that infectious virus likely underlies cardiac complications. However, the pathophysiology of cardiac disease in severe COVID-19 has yet to be clarified. We therefore compared the histologic and molecular findings in human cardiac tissue from fatal COVID-19 cases and age-matched controls. Hematoxylin and eosin (H&amp;E) stains revealed histologic changes in the COVID-19 samples, most notably multifocal endothelial cell swelling and degeneration plus microvascular thrombi. Distribution of SARS-CoV2 RNA and nucleocapsid protein expression was investigated by qRT-PCR and in situ hybridization (ISH). Trace amounts of viral RNA and no nucleocapsid protein were detected in the COVID-19 hearts. However, 7/11 COVID-19 hearts were positive for viral spike protein. Further validation by immunohistochemistry (IHC) showed that viral spike protein was detected in all 11 COVID-19 hearts. Co-expression analysis revealed that viral spike protein localized mostly to the ACE2+ interstitial macrophages/pericytes that were activated as evidenced by increased IL6 and TNFα expression. Previously, we identified a novel arrhythmia mechanism wherein inflammation-induced vascular endothelial dysfunction triggers cardiomyocyte structural remodeling, particularly of intercalated disc (ID) components including connexin-43 (Cx43) gap junctions and Na V 1.5 sodium channels, and thereby promotes arrhythmias. We therefore investigated ID structure in our human samples. Both Cx43 and Na V 1.5 showed marked lateral migration in myocytes of COVID-19 hearts, consistent with previous experiments with inflammatory insults in murine hearts. These findings suggest that the viral spike protein, and not direct infection by SARS-CoV2, results in the pathophysiology of cardiac dysfunction in fatal COVID-19.
Abstract 14369: “July Effect”: Impact of Academic Year Transition on In-Hospital Outcomes of Patients With Cardiac Arrest
Authors: Favour Markson, Richard Orji, Onoriode Kesiena, Ali Horoub, Chidiebele Omaliko
Journal: Circulation (2022)

Introduction: The transition of training to a new Academic year and the beginning of training for new interns and fellows have been suggested to affect the quality of patient care and health care outcomes in critically ill patients, a phenomenon known as the “July Effect” in the United States. Prior studies have shown mixed reports regarding the “July Effect” existence. This study provides an insight into the “July Effect” in patients who suffered Cardiac arrest using a National Database. Methods: We performed a retrospective analysis using the National inpatient sample (2016- 2019). The NIS was searched for hospitalized adult patients with cardiac arrest as a principal diagnosis. We subsequently divided our sample into two cohorts based on the quarter of training (1st quarter, July to September, and the Last quarter of Training April to June). The primary outcome was inpatient mortality, and the secondary outcomes were the length of stay (LOS), total hospitalization charges (THC), and transfer frequency to other acute care facilities. Results: There were 27,940 Patients who suffered a cardiac arrest in the first and last quarter of our study period. Approximately 49.2% (13,755) vs. 50.8% (14,185) patients were identified in the 1st and Last quarters, respectively. There was a similar distribution of Age (63.5 ± 0.2) and Sex (Females) (43%) in both cohorts. There was similar inpatient mortality for patients who presented in both quarters (AOR 1.05, 95% CI 0.855-1.14, p=0.935). There was also no significant difference in LOS (adjusted coefficient -0.19, 95% CI -0.50-0.46, p=0.937), THC (adjusted coefficient 115.9, 95% CI -6483.46 - 6715, p=0.973) and frequency of transfer to other acute care facilities (AOR 0.95, 95% CI 0.82-1.11, p=0.57). Conclusions: This study suggests that the “July Effect” is not apparent in patients who suffered cardiac arrest as there were no significant differences in the rate of in-hospital mortality, length of stay, total hospitalization charges, and frequency of transfer to other acute care facilities.
Abstract 13530: The Impact of COVID-19 Illness Risk on Physical Activity During the Pandemic
Authors: Kelly L Wierenga, Scott E Moore, Susan Ofner, Malissa Mulkey, Jennifer Alwine, Hannah Blake, Eileen Hacker, Pei-Shiun Chang, Susan J Pressler, Susan Perkins
Journal: Circulation (2022)

Introduction: Risk related decision making for physical activity engagement changed during the pandemic. Importantly, life-threatening COVID-19 illness was riskier for adults with many chronic illnesses, including cardiovascular diseases. Determining physical activity level differences between people at high versus low risk for severe COVID-19 is critical for targeting future approaches for improving physical activity and cardiovascular health. Hypotheses: Between March 2020 and May 2021, compared to adults at low risk for severe COVID-19, adults at high risk have 1) greater odds of inactivity; and 2) in adults reporting physical activity, high risk is associated with lower metabolic equivalent of task (MET). Methods: This prospective observational study enrolled English-speaking US adults age 18 years and older. Measures included demographic and health condition surveys, and the International Physical Activity Questionnaire (IPAQ) short form surveys at baseline, with IPAQ repeated at 3, 4, 7, 9, and 13 months. Inactivity was defined as reporting no activity bouts ≥ 10 minutes. Hypotheses testing used a two-part model of physical activity over time simultaneously fitting a logistic model of inactivity and a gamma model of total MET for the physically active while adjusting for age, gender, and race. Results: The sample included n = 687 (mean age = 42.4 ± 15.5, 78% women, 89% white). Odds of inactivity for COVID-19 high risk group was 2 to 4.1 times higher than that of low risk group at baseline and 13 months (Figure 1a). Physically active adults at high risk of severe COVID-19 had MET levels less than the low risk group at baseline (28%, p = .001), 3 (29%, p = .002), and 4 months (30%, p =.005), with no significant differences at later timepoints (see Figure 1b). Conclusions: Inactivity and MET level between group differences varied over time. Disproportionate odds of inactivity and lower MET levels was present primarily early in the pandemic in the high risk group.
Abstract 13103: Defective Vascular Smooth Muscle Cell Tafazzin Impairs Mitochondrial Function and Promotes Atherosclerosis
Authors: Cindy Dong, Alison Finigan, Nichola Figg, Martin Bennett, Emma Yu
Journal: Circulation (2022)

Introduction: Tafazzin acylates immature monolysocardiolipin to form mature cardiolipin. Cardiolipin is the signature phospholipid of the mitochondrial inner membrane required for respiratory efficiency and regulation of apoptosis. Mitochondrial respiration is reduced in atherosclerosis. However, whether tafazzin regulates vascular smooth mucle cell (VSMC) mitochondrial function and contributes to atherosclerosis is unclear. Hypothesis: Tafazzin regulates VSMC mitochondrial function and atherosclerosis development. Methods: We examined tafazzin expression and regulation in human plaques and VSMCs. We determined the in vitro effects of tafazzin using siRNA mediated cell silencing or lentiviral infection to express either tafazzin (Taz) or tafazzin with a transacylase defective mutation (Taz H69Q ). We also generated mice expressing VSMC restricted Taz or Taz H69Q and crossed them with apolipoprotein E deficient mice (SM22α-Taz/ApoE -/- or SM22α-Taz H69Q /ApoE -/- ) to study tafazzin in vivo Results: Tafazzin mRNA and protein is decreased in plaque and plaque VSMCs. MicroRNA 125a-5p expression is increased in plaques, downregulates tafazzin expression and is induced by oxidised low density lipoprotein. Tafazzin silencing and expression of Taz H69Q reduces mitochondrial respiration, decreases ATP content (0.13±0.01nmoles vs 0.21±0.01nmole, n=4), and promotes apoptosis. SM22α-Taz H69Q /ApoE -/- mice showed increased plaque burden (28±2.3% vs 17±2.1%, n=17), increased necrotic core and reduced fibrous cap areas. In contrast, over-expression of tafazzin increases VSMC mitochondrial respiration and protects against apoptosis. SM22α-Taz/ApoE -/- mice showed no change in plaque burden but increased features of plaque stability. SS-31, which binds and stabilises cardiolipin, improves mitochondrial respiration and decreases apoptosis in SM22α-Taz H69Q /ApoE -/- VSMCs. Conclusions: Tafazzin expression is decreased in plaque VSMCs and is negatively regulated by microRNA 125a-5p. Defective tafazzin decreases mitochondrial respiration, increases apoptosis and promotes atherosclerosis. Tafazzin is therefore an important and unrecognised regulator of VSMC mitochondrial function and atherosclerosis.
Abstract 14174: Abnormal Exercise Electrocardiography With Normal Stress Echocardiography is Associated With Increased Subclinical Coronary Atherosclerosis: Insights From the Project Baseline Health Study
Authors: Jessica M Duran, Maggie Nguyen, Francois Haddad, Nicholas Cauwenberghs, Tatiana Kuznetsova, Gerald S Bloomfield, Kenneth Mahaffey, Adrian F Hernandez, Jessica L Mega, Sarah Short, Pamela S Douglas, Svati H Shah, Melissa A Daubert
Journal: Circulation (2022)

Introduction Patients with an abnormal (positive) exercise electrocardiography (ECG), but normal stress echocardiography (+ECG/-Echo) have more adverse cardiac events than patients with a negative ECG and normal stress Echo (-ECG/-Echo). However, it is unclear if ECG/Echo discordance is associated with a greater burden of concurrent subclinical coronary atherosclerosis. Methods In the Project Baseline Health Study (PBHS), participants underwent stress Echo and a coronary artery calcium (CAC) scan. For this PBHS substudy, participants with no known coronary artery disease (CAD) were analyzed by stress result: -ECG/-Echo, +ECG/-Echo, or +Echo (with or without +ECG). Patients with a submaximal stress test, uninterpretable ECG, resting wall motion abnormality, and/or baseline ejection fraction &lt;50% were excluded. Clinical characteristics, exercise performance, and CAC results were compared between the -ECG/-Echo and +ECG/-Echo groups using the chi-squared test and Student’s t-test for categorical and continuous variables, respectively. ANOVA or Kruskal-Wallis test was used, as appropriate, to compare all 3 groups. Results Among 1466 participants, 1357 (92.6%) had a -ECG/-Echo; 85 (5.8%) had a +ECG/-Echo; and 24 (1.6%) had a +Echo. Compared to the -ECG/-Echo group, participants in the +ECG/-Echo group were older with shorter exercise duration, but younger with fewer risk factors than participants with a +Echo. The median 10-year ASCVD risk score was 2% for -ECG/-Echo, 3% for +ECG/-Echo, and 10% for +Echo (p&lt;0.001). Greater abnormalities by exercise stress Echo were associated with an increased burden of concurrent coronary atherosclerosis as assessed by CAC score and CAC volume (Table). Conclusions Individuals with positive exercise ECG, even with normal stress Echo, have a higher burden of subclinical coronary atherosclerosis than those with -ECG/-Echo, which may explain the increased risk for adverse cardiac events in the +ECG/-Echo population.
Abstract 14084: Safety and Outcomes of Percutaneous Coronary Intervention in Patients Presenting With Acute Coronary Syndrome With Prior Liver Transplantation
Authors: Abdelrhman Abumoawad, Mohamed Ahmed, Paramdeep Baweja, Kamal gupta
Journal: Circulation (2022)

Background: There is a paucity of data about the outcomes of performing Percutaneous coronary intervention (PCI) for Liver transplant (LT) patients presenting with acute coronary syndrome (ACS). Methods: We queried the national readmission database for patients who underwent PCI hospitalized between 2016 and 2019, patient were classified into two groups based on prior LT status. International classification of disease codes (ICD-10) were used for diagnosis and procedures codes. Our outcomes were In-hospital mortality and 90-day readmission rate. A multivariate adjusted regression model was performed to risk adjust for predictors of 90-day readmission (all-cause). Results: A total of 1400,861 patients underwent PCI between the years 2016 and 2019 for ACS and underwent PCI. 1,532 patients had a history of LT (0.1%). Hospitalized patients with prior LT were of similar age (65.2 ±0.31 vs 65.3 ±0.04 years, p=0.9), and less likely to be women (20.8.6% vs. 32.5%, p&lt;0.01) compared with those without prior LT history. Hospitalized patients with prior LT had similar In-hospital mortality rate (3.9% vs 2.9%, p=0.3), shock (5.3% vs 4.5%, p=0.34), and Mechanical circulatory support utilization rate (4.9% vs 4.3%, p=0.452) but longer length of stay (5.8±0.3 vs 4.1±0.02, P&lt;0.001) compared to the cohort that had no prior LT. Patients with prior LT had a higher readmission rate within 90 days 29.6% vs 19.4%, p= 0.001), and were less likely to have repeat PCI in the readmission (7.9% vs 12.3%, p&lt;0.001), however more likely and acute kidney injury. Both cohorts had similar rates of acute heart failure exacerbation, bleeding complications, or in-hospital mortality in the readmission. Conclusion: There was no significant difference in mortality between both cohorts, however, readmission rate was higher in the LT cohort, Further studies exploring these differences may help to mitigate these readmissions.
Abstract 12986: Internal Iliac Artery Occlusion With the Amplatzer Vascular Plug During Endovascular Repair of Large Abdominal Aortic Aneurysm
Authors: Cameron B Tuazon, Angela Chavira, M. Rubayat Rahman, Ankush Lahoti
Journal: Circulation (2022)

Background: Retrograde blood flow from the internal iliac artery resulting in a type II endoleak is a challenging complication of endovascular aorto-iliac aneurysm repair. Several methods have been developed to address this concern. We present a case where the Amplatzer vascular plug was used to embolize the internal iliac artery in a patient undergoing aorto-iliac stent-grafting with extension of the graft into the external iliac artery. Case: A 67-year-old male presented with abdominal pain. Abdominal contrast computed tomography confirmed a large infrarenal abdominal aortic aneurysm (AAA) measuring 100 mm across, extending into the common iliac artery on the right and the external iliac artery on the left, with perianeurysmal fat stranding indicating impending rupture. The patient was taken emergently to the operating room. Vascular access was obtained through bilateral common femoral arteries. The left internal iliac was occluded with an Amplatzer 16 mm by 12 mm vascular plug, with excellent angiographic apposition. A bifurcated aorto-iliac graft was then sequentially deployed to repair the aneurysm. Final angiography showed patent renal arteries with no endoleak. The patient was discharged home the following day. Discussion: Embolization of the internal iliac artery is indicated in endovascular aorto-iliac aneurysm repair to prevent endoleak formation. Traditionally performed with coils, the Amplatzer vascular plug has emerged as a safe and effective alternative, with the added advantage of recoverability prior to definitive release. Conclusion: Endovascular repair of an AAA must consider the complication of endoleak formation. In this case, the use of an Amplatzer vascular plug was successful in preventing a type II endoleak from the internal iliac artery. Panel A. 3D reconstruction of aneurysm anatomy; Panel B. Angiogram showing final result of endovascular repair with successful occlusion of the left internal iliac artery
Abstract 13135: Mir455 Targets the Repeated Domains of <i>Lpa</i> Open Reading Frame and Lowers Its Expression and The Secretion of Apolipoprotein (a) From Human Cells
Authors: Kevin Chemello, Gilles Lambert
Journal: Circulation (2022)

Introduction: Lipoprotein (a) [Lp(a)] is a peculiar lipoprotein species containing a unique glycoprotein apolipoprotein(a) [apo(a)] encoded by the LPA gene. Lp(a) is causatively, independently and significantly associated with CAD and calcified aortic valve stenosis. MiRs are approximately 22 nucleotides in length and work by inducing RNA silencing, thus reducing target genes expression. The influence of these regulatory elements on the expression of LPA remains unknown. Hypothesis: Apo(a) and Lp(a) plasma levels are genetically regulated by miRs. Method: A prediction software was used to identify miR candidates targeting the human LPA mRNA open reading frame (ORF). We investigated the selected candidates by transfecting these miRs (i) in HEK293 cells stably expressing a short LPA isoform (i.e. 17 KIV domains) and (ii) in the Hep3B human hepatoma cell line that endogenously express LPA . A validated siRNA targeting LPA and a scrambled siRNA were used as positive and negative controls, respectively. LPA expression was assessed by RT-qPCR. Apo(a) protein expression and secretion in the culture medium were assessed by Western Blot and ELISA, respectively. Results: We identified four miR candidates (miR22, miR194, miR218, and miR455) based on sequence complementarity between their seed region and the LPA mRNA ORF. Compared with the negative control, only miR455 significantly reduced LPA mRNA expression (-67±8%) as well as apo(a) intracellular abundance (-41±9%) and apo(a) secretion (-36±9%) in the culture medium ( p&lt;0.001 , all). Similar reductions were observed with the positive siRNA control (-77±4%, -41±11%, -53±11 %, p&lt;0.001 all, respectively). No significant effect on LPA expression was seen with the three other miR candidates. Conclusion: These in vitro results suggest that at least one human miR has the potential to regulate the circulating levels of Lp(a) in vivo . This will be verified by measuring miR455 abundance in liver and plasma samples from individuals with high vs. low Lp(a) plasma concentrations. Our study also underlines that targeting LPA with interfering RNAs is likely a regulatory process occurring in humans.
Abstract 13046: Bleeding Complications During Cardiac Electronic Device Implantation With Novel Oral Anticoagulants versus Vitamin K Antagonist : A Systematic Review and Meta-Analysis
Authors: Maryam Saleem, Faysal Alhasan, Nataly Akbarshahi, verda arshad, Pooneh Nabavizadeh, Jackson Walker, Alexandru Costea, Duc H Do, Muhammad Rizwan Afzal, Raul Weiss
Journal: Circulation (2022)

Introduction: Pocket hematoma is a feared complication of cardiac implantable electronic device (CIED) placement. About half the patients undergoing the procedure are on anticoagulation with consequent increased frequency of device-pocket hematoma. The risk of hematoma is variable based on the type of anticoagulation therapy. The purpose of this study was to compare the risk of device-hematoma in patients on interrupted novel oral anticoagulants (NOAC) versus uninterrupted vitamin K antagonists (VKA) during the peri-operative period. Methods: We performed a meta-analysis using electronic literature search to retrieve studies with CIED surgery on uninterrupted VKA versus interrupted NOAC (range 12-96 hours). Primary outcome of interest was pocket-hematoma. Outcomes were pooled under random-effects meta-analyses and reported as risk ratios (RRs) and 95% CIs. 5 studies with low heterogeneity (I 2 =14%), 4 observational and 1 post-hoc analysis of a randomized trial, were included. 1002 patients NOAC group=376 and VKA group=626 were followed for 4-6 weeks. Results: Baseline characteristics were similar, mean age 71 years and 71% male across both groups. There was no significant difference in endpoints: pocket hematoma (major and minor) {RR 0.74 (0.43-1.29), P=0.29}; major hematoma {RR 0.53 (0.24-1.19), P=0.13}; hematomas with new implants {RR 0.82 (0.46-1.48), P=0.51}; hematomas with generator changes {RR 1.90 (0.84-4.31), P=0.12}; hematomas with device-upgrade {RR 0.41 (0.15-1.07), P=0.07}; major bleed {RR 0.18 (0.03-1.09), P=0.06}; pericardial effusion {RR 1.01 (0.13-8.19), P=0.67}(Fig 1). One study reported peri-implantation infection (n=4/311 NOAC, n=2/467 VKA). One patient out of all 5 studies had systemic thromboembolism in each group (1/837 NOAC, 1/1000 VKA). Conclusion: Interrupted NOAC use is not associated with a higher risk of pocket hematoma compared to uninterrupted VKA after CIED placement.
Abstract 13429: A Systematic Review and Meta-Analysis of Comparative Studies of Postoperative Atrial Fibrillation in Obstructive Sleep Apnea Patients Undergoing Coronary Artery Bypass Grafting
Authors: Avilash Mondal, Nishanth Katukuri, Adhvithi Pingili, Koushik Sanku, BORZOO TAJDIN, Tamer Zahdeh, Akhila S Cherukuri, HAMIDREZA JALILI, Pooriya Bahadoran, Sashwath Srikanth, Rupak Desai
Journal: Circulation (2022)

Background: Post-CABG Atrial Fibrillation (PCAF) is linked to higher mortality, morbidity, and healthcare costs. Obstructive Sleep Apnea (OSA) has been studied as a risk factor for PCAF in a few studies. In this study, we sought to review and analyze the association between OSA and PCAF. Methods: We systematically searched PubMed, Scopus, and EMBASE for studies on OSA as predictors of PCAF using relevant keywords through June 2022. Random effects models were used to estimate pooled rates of PCAF with subgroup analysis. I 2 statistics were used to report inter-study heterogeneity. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate. Results: A total of 15 (N= 534387) studies were included between 2008-2021 in our Systematic review/Meta-analysis (Median follow-up duration: 29 days; mean age: 59-72 years; Males: 68.4%). 8 US-based studies, with the rest from Europe and South Asia, were included. A total of 34654 PCAF events were recorded. Pooled analysis of unadjusted (OR 1.23, 95%CI 1.07-1.42, p&lt;0.01) and adjusted (1.24, 95%CI 1.10- 1.40, p&lt;0.01) odds of PCAF was higher in OSA vs non-OSA cohorts. Subgroup analysis indicated greater risks of PCAF in prospective studies (OR 1.83, 95% CI 1.24-2.71 p 0.01) but not in retrospective studies. Rates of PCAF were higher in studies reported from other countries compared to the US (1.24 vs 1.18, p&lt;0.001) and with longer follow-up (&gt;3 years) compared to those with shorter follow-up (1 month) duration. Conclusions: In this meta-analysis, OSA predicted a nearly 25% higher risk of developing PCAF. Prospective studies assessing the long-term impact of OSA on cardiovascular risk after CABG are warranted to curtail worse outcomes.